Systems Biology in the Study of Neurological Disorders: Focus on Alzheimer's Disease

Article excerpt

Systems biology approaches may be useful for studying the mechanisms underlying alcohol's harmful effects on the brain. Such approaches already are used in the study of Alzheimer's disease (AD), a progressive neurodegenerative disorder that, with the overall increase in life expectancy, will affect an increasing proportion of the population and become an increasingly serious public health concern. Systems biology approaches such as complementary DNA (cDNA) microarray analyses have helped identify several genes whose expression is altered in patients exhibiting the earliest stages of AD. Several of these genes are involved in the release of messenger molecules from the ends of nerve cells (i.e., in synaptic vesicle functioning), and their particular role in AD must be investigated further using conventional molecular biological approaches. Similarly, protein array analyses have identified candidate proteins that may play a role in the development of AD. Finally, proteomic approaches, such as certain mass spectrometry techniques, have been used to search for biomarkers of the progression from normal cognitive functioning to mild cognitive impairment and AD, which eventually may allow early and reliable diagnosis of the disease. These approaches already have yielded some candidate molecules whose validity and reliability as biomarkers of AD, however, still need to be confirmed. KEY WORDS: Alzheimer's disease (AD); cognitive impairment; dementia; genetic risk factors; biomarkers; complementary DNA (cDNA) microarray analysis; protein array analysis; systems biology; proteomics; alcohol and other drug effects (AODEs)

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As the articles in this issue ofAlcohol Reseawh &Hedth demonstrate, systems biology approaches increasingly are being used in research on several disorders associated with excessive alcohol use. One of the organs most severely affected by excessive alcohol consumption is the brain, and longterm heavy drinking has serious detrimental effects on brain structure and functioning. For example, alcoholics often exhibit various degrees of cognitive impairment and, in the most severe cases, can develop alcoholic dementia. In addition, some alcoholics develop a condition known as Wemicke-Korsakoffsyndrome, which is characterized by shrinkage of brain tissue and memory loss (i.e., anterograde amnesia). Systems biology approaches may be useful for studying the mechanisms underlying alcohol's harmful effects on the brain as well as its consequences and ultimately aid in the diagnosis of alcohol-related neurological deficits. Although these approaches only are beginning to be used in research on alcohol-related neurological disorders, they already have been employed in the study of other neurological disorders, most prominently Alzheimer's disease (AD), for which genomic and, particularly, proteomic approaches may help identify biomarkers that allow physicians to reliably diagnose the disease at an early stage. Accordingly, AD can be used as an example to illustrate the potential of similar approaches for the understanding and perhaps diagnosis of alcohol-related neurological deficits. Furthermore, this research on AD may be relevant to alcohol research because some investigators have suggested that alcohol use may influence the risk of developing AD, as certain brain-signaling systems are affected both by alcohol use and by AD (Tyas 2001). To date, however, epidemiological studies have not found strong evidence to support an association between alcohol use and AD (Tyas 2001).

After providing a brief background on AD, this article describes the systems biology approaches that have been used in the study of AD and summarizes the most relevant findings and perspectives. Although this discussion focuses only on one particular disorder and on the work of only a few research groups, it highlights the potential of systems biology approaches for improving diagnosis and understanding of neurological disorders in general, including those associated with alcoholism. …